The objective of this proposal is to acquire a high-resolution ultrasound imaging system for use in biomedical research using small animals spanning the size of mice embryos to rabbits. This first and only commercially available high-frequency, high-resolution digital imaging platform with high-frequency linear array technology is capable of imaging live small animals at axial and lateral resolutions of 30 [unreadable]m and 65 [unreadable]m, respectively with unprecedented imaging depth of up to 36mm. This system has diverse new imaging functions such as 3D imaging integrated with color Doppler, ECG-gated image registration, left-ventricular (LV) function analysis, strain/strain rate analysis, and contrast imaging with harmonics. The system can assess whole organ scale functions to cellular level bioactivity. Anatomical, functional (flow), physiological and molecular data are available from in vivo imaging in real time. The digital system allows raw data access through radio frequency (RF) data capturing modules, which is critical to off-line data analysis using new image processing technologies developed at our institution. This system will be of enormous value to a wide spectrum of interdisciplinary rodent research. As a user group, we have 9 independent PIs with active NIH R01 equivalent support and 5 independent PIs with other support from different NIH funding mechanisms and also from other funding institutes. The participating PIs are from different departments across the University of Pittsburgh campus, spanning the Departments of Surgery, Cell Biology and Physiology, Pharmacology, Environmental and Occupational Health, Bioengineering, the Cardiovascular Institute (CVI), the Hillman cancer Center, and the McGowan Institute of Regenerative Medicine. The projects for which the imaging system is needed employ in-vivo preclinical testing in small animals and address topics in cardiac, vascular, and respiratory diseases, cancer, and engineered tissue and regenerative medicine. To promote cost effectiveness in maintenance and upgrade, optimize the sharing arrangement, foster a collaborative multidisciplinary environment, the system will be integrated into the Cardiovascular Institute's Center for Ultrasound Molecular Imaging and Therapeutics, (directed by Dr Villanueva, major user of the system) where the ultrasound laboratories of the PI (Dr. Kim) are located. An advisory committee has been formed and guidelines established by which the imaging system can be shared among the users and by which new users can gain access to and training for the system. Our scheme for managing the system is designed to ensure the best possible use of the system and maximum contribution for the listed projects and to continuously identify other NIH projects that will benefit from this system. The acquisition of the requested ultrasound animal imaging system will be of enormous value to not only to current NIH-funded projects across the campus of the University of Pittsburgh but also to the development of future NIH projects. The Cardiovascular Institute is fully committed to the support of maintenance, personnel, space, and resources required for long-term use of the system. PUBLIC HEALTH RELEVANCE: With no appropriate in-vivo imaging tool, most of the endpoints utilized in in-vivo studies are non-survival, increasing significantly the number of experiments, undesired variation between animal groups, and the time of the research. Non-invasive in vivo imaging tools can minimize the number of animals and provide the more clinically relevant data in real time. One of the most relevant, clinically useful endpoints that can be obtained in the intact, live organism, is real-time ultrasound assessment. The first and only commercially available highdefinition digital imaging platform, Vevo 2100 by VisualSonics, is capable of real-time imaging of live small animals from zebra fishes or mice embryos to rabbits at the resolution of the typical size of single cell. The acquisition of the requested system will be of enormous value to not only to current NIH-funded projects across the campus at University of Pittsburgh but also development of many other future NIH projects.